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Phase II multicenter study of UV irradiation with UvadexTM outside of the body plus standard steroid treatment for high risk acute Graft-versus-Host Disease

Phase 1
Conditions
ew onset high risk acute GvHD following allogeneic SCT
MedDRA version: 20.0Level: LLTClassification code 10018653Term: Graft-versus-host disease <GVHD>System Organ Class: 100000004870
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Registration Number
EUCTR2019-000894-22-DE
Lead Sponsor
Department of Stem Cell Transplantation - University Medical Center Hamburg-Eppendorf
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
72
Inclusion Criteria

1. New onset high risk acute GvHD (Ann Arbor score 2/3 as defined in Appendix A) following allogeneic SCT. Any clinical severity (Glucksberg grade I-IV) is eligible.
2. Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.
3. No prior systemic treatment for acute GvHD except for a maximum of 7 days of methylprednisolone =2 mg/kg/day (or IV Methyprednisolone equivalent) during the period from the initiation of systemic steroid treatment for acute GvHD until study therapy begins. Topical skin steroid treatment and non-absorbable oral steroid treatment for GI GvHD are permissible.
4. Age 18 years or older.
5. Platelet count > 25.000 (including platelet support)
6. Eastern Coorperative Oncology Group (ECOG) score of 0=2 unless due to aGvHD
7. Negative pregnancy test within 10 days before start of study if the patient is a woman of child-bearing age
8. Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGvHD within 3 days before screening.
9. ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days before screening.
10. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol (see section 11).
11. Written informed consent from patient.
12. Biopsy of acute GvHD target organ is strongly recommended but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not start ECP within 5 working days of initiation of systemic steroid treatment for acute GvHD are not permitted to par-ticipate.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

1. Progressive or relapsed malignancy
2. Uncontrolled active infection
3. Patients with chronic GvHD
4. History of or current diagnosis of progressive multifocal leu-koencephalopathy (PML)
5. Pregnant or nursing (lactating) women
6. Use of other drugs for the treatment of acute GvHD apart from on-going GvHD prophylaxis and corticosteroids
7. Patients on dialysis
8. Patients requiring ventilator support
9. Evidence of known infection with human immunodeficiency virus (HIV) or active hepatitis B
10. Investigational agent within 30 days of enrollment without approval from the Sponsor-Investigator (PI). (Off-label use of medication is not considered investigational unless in context of a formal study)
11. History of allergic reaction to 8-MOP
12. Concomitant diagnosis of malignant melanoma or basal cell carci-noma
13. Hypersensitivity or allergy to both heparin and citrate products (if hypersensitive or allergic only to one, exclusion does not apply)
14. Inability to tolerate extracorporeal volume shifts associated with ECP
15. Presence of aphakia
16. History of splenectomy
17. Leucocyte count > 25.000/ul
18.Coagulopathy
19. Known photosensitive disease like systemic lupus erythematosus, porphyrias or albinism

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To improve day 28 GvHD complete response rate for high risk (Ann Arbor Score 2/3) GvHD patients from the historical rate of 37% to 52% by treatment with ECP and high dose systemic corticosteroids (2 mg/kg).<br>;Secondary Objective: To decrease 6-month NRM from the historical rate of 30% to 20% in patients treated on this clinical trial.;Primary end point(s): The primary endpoint for this clinical study is the proportion of complete response (that is, the per-cent of patients with skin, liver, and GI GvHD all stage 0) at day 28 of study treatment.;Timepoint(s) of evaluation of this end point: At day 28 of study treatment
Secondary Outcome Measures
NameTimeMethod
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